Summary
Neuronal transmitter stores of the rat phrenic nerve were labelled by an incubation with [3H]choline. Release of [3H]acetylcholine was elicited either by a short (100 pulses, 5 Hz) or by a long (1500 pulses, 5 or 25 Hz) period of electrical nerve stimulation. Pirenzepine and dicyclomine enhanced transmitter release evoked by the short stimulation period. Both antagonists reduced transmitter release evoked by the long stimulation period. Pirenzepine reduced transmitter release at low concentrations (1 nmol/l) whereas a higher concentration was necessary for the enhancing effect; the opposite pattern was found for dicyclomine. A low concentration of oxotremorine (10 nmol/l) enhanced and a high concentration (1 μmol/l) reduced transmitter release evoked by the short stimulation period. Both effects could be prevented by a low concentration of pirenzepine (10 nmol/l). It is concluded that facilitatory and inhibitory muscarine receptors are present on the motor nerve. A short stimulation period activates predominantly the negative muscarinic feedback, whereas during a long period of continuous nerve stimulation the positive muscarinic feedback mechanism is additionally activated. Both the facilitatory and inhibitory receptors might be regarded as M1-receptors but differences in the pharmacological properties between both receptor populations appear possible.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abbs ET, Joseph DN (1981) The effects of atropine and oxotremorine on acetylcholine release in rat phrenic nerve-diaphragm preparations. Br J Pharmacol 73:481–483
Birdsall NJM, Hulme EC (1985) Multiple muscarinic receptors: Further problems in receptor classification. Trends Autonom Pharmacol 3:17–34
deJonge A, Doods HN, Riesbos J, van Zwieten PA 1986 Heterogeneity of muscarinic binding sites in rat brain, submandibular gland and atrium. Br J Pharmacol 89:551P
Eglen RM, Whiting RL (1986) Muscarinic receptor subtypes: a critique of the current classification and a proposal for a working nomenclature. J Autonom Pharmacol 5:323–346
Fosbraey P, Johnson ES (1980) Modulation by acetylcholine of the electrically-evoked release of [3H]acetylcholine from the ileum of the guinea-pig. Br J Pharmacol 69:145–149
Ganguly DK, Das M (1979) Effects of oxotremorine demonstrate presynaptic muscarinic and dopaminergic receptors on motor nerve terminals. Nature 278:645–646
Giachetti A, Giraldo E, Ladinsky H, Montagna E (1986) Binding and functional profiles of the selective M1 muscarinic receptor antagonists trihexyphenidyl and dicyclomine. Br J Pharmacol 89:83–90
Greenwood B, Read NW, Hardcastle PT, Hardcastle J (1984) Effect of secoverine and atropine on intestinal secretion and motor activity in the rat small intestine in-vivo. J Pharm Pharmacol 36:100–106
Gundersen CB, Jenden DJ (1980) Oxotremorine does not enhance acetylcholine release from rat diaphragm preparations. Br J Pharmacol 79:8–10
Hammer R, Berrie CP, Birdsall NJM, Burgen ASV, Hulme EC (1980) Pirenzepine distinguishes between different subclasses of muscarinic receptors. Nature 283:90–92
Kilbinger H, Nafziger M (1985) Two types of neuronal muscarine receptors modulating acetylcholine release from guinea-pig myenteric plexus. Naunyn-Schmiedeberg's Arch Pharmacol 328:304–309
Kilbinger H, Wessler I (1980) Inhibition by acetylcholine of the stimulation evoked release of [3H]acetycholine from the guinea-pig myenteric plexus. Neuroscience 5:1331–1340
Lindmar R, Löffelholz K (1987) Muscarinic M1-receptors mediate the negative inotropic effect of methacholine in chicken but not in guinea-pig atria. Eur J Pharmacol 139:359–360
Muscholl E (1979) Presynaptic muscarine receptors and inhibition of release. In: Paton DM (ed) The release of catecholamines from adrenergic neurons. Pergamon Press, Oxford New York, 87–110
Mutschler E, Gmelin G, Moser U, Wess J, Lambrecht G (1987) Structure-activity relationships of drugs acting selectively at different muscarinic receptors. In: Rand MJ, Raper C (eds) Pharmacology. Elsevier Press, Amsterdam, pp 67–75
Mutschler E, Lambrecht G (1984) Selective muscarinic agonists and antagonists in functional tests. Trends Pharmacol Sci (Suppl) 5:39–44
Peralta EG, Winslow JW, Ashkenazi A, Smith DH, Ramachandran J, Capon DJ (1988) Structural basis of muscarinic acetylcholine receptor subtype diversity. Trends Pharmacol Sci (Suppl) 9:6–11
Schwörer H, Kilbinger H (1988) Enhancement of guinea-pig intestinal peristalsis by blockade of muscarinic M1-receptors. Br J Pharmacol 93:715–720
Somogyi GT, Vizi ES, Chaudhry IA, Nagashima H, Duncalf D, Foldes FF, Goldiner PL (1987) Modulation of stimulation-evoked release of newly formed acetylcholine from mouse hemidiaphragm preparation. Naunyn-Schmiedeberg's Arch Pharmacol 336:11–15
Wallenstein S, Zucker CL, Fleiss JI (1980) Some statistical methods useful in circulation research. Circ Res 47:1–9
Wessler I, Karl M, Mai M, Diener A (1987) Muscarine receptors on the rat phrenic nerve, evidence for positive and negative muscarinic feedback mechanisms. Naunyn-Schmiedeberg's Arch Pharmacol 335:605–612
Wessler I, Kilbinger H (1986) Release of [3H]acetycholine from a modified rat phrenic nerve-hemidiaphragm preparation. Naunyn-Schmiedeberg's Arch Pharmacol 334:357–364
Wessler I, Steinlein O (1987) Differential release of [3H]acetylcholine from the rat phrenic nerve-hemidiaphragm preparation by electrical nerve stimulation and by high potassium. Neuroscience 22:289–299
Author information
Authors and Affiliations
Additional information
This work was supported by the Deutsche Forschungsgemeinschaft. The paper contains part of the Dr. med. thesis of A. D. and M. O.
Send offprint requests to I. Wessler at the above address
Rights and permissions
About this article
Cite this article
Wessler, I., Diener, A. & Offermann, M. Facilitatory and inhibitory muscarine receptors on the rat phrenic nerve: effects of pirenzepine and dicyclomine. Naunyn-Schmiedeberg's Arch Pharmacol 338, 138–142 (1988). https://doi.org/10.1007/BF00174861
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00174861